2026-10-22T10:36:40Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/48812021-11-10T09:38:19Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925
Repositorio Institucional de la Universidad de Burgos
author
Kotev, Martin .
author
Manuel Manresa, Pilar .
author
Hernando Santa Cruz, Elsa
author
Soto Cerrato, Vanessa
author
Orozco, Modesto .
author
Quesada Pato, Roberto
author
Pérez Tomás, Ricardo
author
Guallar, Victor
2018-08-24T09:48:45Z
2018-08-24T09:48:45Z
2017-08
1549-9596
http://hdl.handle.net/10259/4881
10.1021/acs.jcim.7b00178
Combining computational modeling, de novo compound synthesis, and in vitro and cellular assays, we have performed an inhibition study against the enhancer of zeste homolog 2 (EZH2) histone-lysine N-methyltransferase. This enzyme is an important catalytic component of the PRC2 complex whose alterations have been associated with different cancers. We introduce here several tambjamine-inspired derivatives with low micromolar in vitro activity that produce a significant decrease in histone 3 trimethylation levels in cancer cells. We demonstrate binding at the methyl transfer active site, showing, in addition, that the EZH2 isolated crystal structure is capable of being used in molecular screening studies. Altogether, this work provides a successful molecular model that will help in the identification of new specific EZH2 inhibitors and identify a novel class of tambjamine-derived EZH2 inhibitors with promising activities for their use in cancer treatment.
eng
Inhibition of human enhancer of zeste homolog 2 with tambjamine analogs
info:eu-repo/semantics/article
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URL
https://riubu.ubu.es/bitstream/10259/4881/1/Kotev-JCIM_%202017.pdf
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Kotev-JCIM_ 2017.pdf
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https://riubu.ubu.es/bitstream/10259/4881/3/Kotev-JCIM_%202017.pdf.txt
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Kotev-JCIM_ 2017.pdf.txt